Microbiota; Mucosal Immunology; Intestine; Mucosal Infection; Innate Immunity; Pathogenic bacteria
Cuenca Miguelangel, Pfister Simona P, Buschor Stefanie, Bayramova Firuza, Hernandez Sara B, Cava Felipe, Kuru Erkin, Van Nieuwenhze Michael S, Brun Yves V, Coelho Fernanda M, Hapfelmeier Siegfried (2016), D-Alanine-Controlled Transient Intestinal Mono-Colonization with Non-Laboratory-Adapted Commensal E. coli Strain HS., in PloS one
, 11(3), 0151872-0151872.
Balmer Maria L., Ma Eric H., Bantug Glenn R., Grählert Jasmin, Pfister Simona, Glatter Timo, Jauch Annaïse, Dimeloe Sarah, Slack Emma, Dehio Philippe, Krzyzaniak Magdalena A., King Carolyn G., Burgener Anne-Valérie, Fischer Marco, Develioglu Leyla, Belle Réka, Recher Mike, Bonilla Weldy V., Macpherson Andrew J., Hapfelmeier Siegfried, Jones Russell G., Hess Christoph (2016), Memory CD8+ T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function, in Immunity
, 44(6), 1312-1324.
Moor Kathrin, Wotzka Sandra Y, Toska Albulena, Diard Médéric, Hapfelmeier Siegfried, Slack Emma (2016), Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species., in Frontiers in immunology
, 7, 34-34.
Gomez de Agüero Mercedes, Ganal-Vonarburg Stephanie C, Fuhrer Tobias, Rupp Sandra, Uchimura Yasuhiro, Li Hai, Steinert Anna, Heikenwalder Mathias, Hapfelmeier Siegfried, Sauer Uwe, McCoy Kathy D, Macpherson Andrew J (2016), The maternal microbiota drives early postnatal innate immune development., in Science (New York, N.Y.)
, 351(6279), 1296-302.
Balmer Maria L., Schürch Christian M., Saito Yasuyuki, Geuking Markus B., Li Hai, Cuenca Miguelangel, Kovtonyuk Larisa V., McCoy Kathy D., Hapfelmeier Siegfried, Ochsenbein Adrian F., Manz Markus G., Slack Emma, Slack Emma, Macpherson Andrew J. (2013), Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling, in Journal of Immunology
, 193(10), 5273-5283.
The research described in this proposal will use a novel reversible intestinal infection model that I recently invented (Hapfelmeier et al., 2010; Science 328:1705-1709) for the detailed study of the differences between intestinal commensal and pathogen immune recognition. In my earlier work this system allowed fully reversible intestinal exposure of germ-free animals with live commensal bacteria so that the bacterial-induced intestinal immunity could be uncoupled from persistent bacterial colonization and studied in the again germ-free system. This permitted detailed quantitative and temporal analysis of host responses to encounters of live commensal bacteria. In the research project described here, the reversible bacterial colonization model will be extended to produce a model of reversible intestinal infection with intestinal pathogenic bacteria to uncouple pathogen immunity from pathogen immune evasion. Most microbes we encounter are commensal bacteria that benignly colonize the intestinal lumen. The immune system is well adapted for host-commensal mutualism, and mutualism breakdown, as in inflammatory bowel disease, is rare. In contrast, pathogenic bacterial encounters are less frequent and countered with anti-pathogen immune defense and inflammation. During infection, the host-pathogen relationship is a competition between anti-bacterial immunity and pathogen immune evasion - the latter is well studied, the former largely in systems where the pathogen proliferates and immune evasion overlays immunity. There is the need to experimentally uncouple pathogen immunity and pathogen immune evasion. Our novel approach to this permits the detailed comparative analysis of pathogen and commensal immune induction and will shed new light on the mechanisms of pathogen versus commensal immune recognition. This knowledge is critical for the design of efficient bacterial vaccines and the understanding of the abnormal immune responses directed against commensal microbes in chronic inflammatory diseases.